通过细菌代谢物对肠道CX3CR1+细胞的依赖GPR31的突
Naoki Morita1,2,3, Eiji Umemoto1,2,3, Setsuko Fujita4
1Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
Nature
|January 25, 2019
概括
细菌代谢物Pyruvic和乳酸通过GPR31在小肠中触发免疫细胞突. 这增强了对沙门氏菌感染的免疫反应和抵抗力.
科学领域:
- 免疫学
- 微生物学
- 胃肠病学
背景情况:
- 表达CX3CR1 (CX3CR1+细胞) 的小肠单核细胞对于调节免疫反应至关重要.
- 这些细胞通过向肠膜扩展树突来捕获光抗原.
- 诱导肠道CX3CR1+细胞突起的精确机制在很大程度上是未知的.
研究的目的:
- 阐明细菌代谢物诱导肠道CX3CR1+细胞突起的机制.
- 研究G蛋白结合受体31 (GPR31) 在这个过程中的作用.
- 确定代谢物诱导的突在免疫反应和病原体耐药性的影响.
主要方法:
- 研究了细菌代谢产物 (酸,乳酸) 对小鼠肠道CX3CR1+细胞的影响.
- 使用缺乏GPR31的小鼠 (Gpr31b-/-) 来评估受体的作用.
- 分析了无特定病原体和无细菌小鼠的小肠内容.
- 向野生型和Gpr31b-/-型小鼠口服乳酸盐和酸盐.
- 评估了对沙门氏菌 Typhimurium 感染的免疫反应和抵抗力.
主要成果:
- 通过GPR31在CX3CR1+细胞中诱导树突突突起的Pyruvic酸和乳酸被确定为关键的细菌代谢物.
- 缺乏GPR31的小鼠表现出有缺陷的树突起.
- 在野生型小鼠中,口服乳酸盐和酸盐增强了树突突,但不是Gpr31b-/ - 小鼠.
- 在野生小鼠中,用乳酸盐或酸盐治疗显著增强了免疫反应和沙门氏菌耐药性.
结论:
- 由肠道细菌产生的乳酸盐和酸盐诱导GPR31介导肠道CX3CR1+细胞的突.
- 这种机制增强了免疫反应,并提供了对沙门氏菌等肠道感染的抵抗力.
- 突出了细菌代谢物与肠道免疫系统的抗原采样能力之间的直接联系.
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